Airflow into the lungs is proportional to the negative pressure generated by the contraction of the inspiratory muscles (the diaphragm and chest wall muscles) and inversely related to the resistance within the airway. Airflow ceases when the distending negative pressure is less than the elastic recoil of the lungs themselves (equal pressure point) and the respiratory cycle begins again. The duration of inspiration is therefore positively related to pressure. The volume of air moved is finite and reflects individual vital capacity. Airflow ceases when total lung capacity is reached and no more air is available to achieve flow. At this point the inspiratory muscles are in their fully shortened position.
Control of air flow and the depth of breathing is known to be important in therapy. Treatment of patients with pulmonary disease, for example, commonly involves administration of drugs directly into the lungs and in addition to the particle size of the drug, inspiratory flow rate and breathing patterns are known to have an effect on determining the depth of penetration of the administered drug into the lungs. Airway clearance techniques for clearing sputum retained in the airways of the lungs arising, for example, from pulmonary inflammation or cystic fibrosis, also commonly rely on changes in the depth of inspiration and augmentation of shearing forces to facilitate movement of retained secretions from the periphery of the lung to the central airways where they can be expectorated. Respiratory muscle training methods involving the subject meeting a target airflow within progressively reduced time periods in order to strengthen and train the respiratory muscles are also well known.
A number of devices which can be used to modify air flow into or out of the lungs have been proposed. Examples include devices offering resistance to inspiration which may be used in inspiratory muscle training techniques such as the Powerbreathe and Threshold trainers (see, for example, Larson et. al., American Review of Respiratory Disease 138, 689-96 (1998), Hart et. al, Respiratory Medicine 536-531 (1995)). These require the user to breathe against a pre-set spring valve which requires a certain pressure to open it. Disadvantages associated with these devices are that they do not fix breathing frequency, provide little biofeedback and once the valve is open, they offer no further resistance. Resistive devices without a valve, such as the Pflex trainer (Chatham, British Journal of Therapy and Rehabilitation 2(1), 31-35 (1995)) are also known. These type of devices increase resistance by having subjects breathe through a progressively smaller hole but as flow, pressure and timing are not fixed, a training response is not ensured.
Other respiratory training devices known in the art include the RT2 and Trainair devices. In these devices resistance is applied by the use of a fixed 2 mm leak within the manometer used. They are capable of providing computerised biofeedback and have been used in through-range training, applying fixed load training with resistance applied from residual volume (breathing all the way out) to total lung capacity (breathing all the way in) in healthy subjects and patient groups. As the leak is fixed, however, this directly affects the nature of the training by altering and fixing the velocity at which the contracting inspiratory muscles shorten.
Software has been developed to assist in analysing breathing patterns and providing feedback when a subject is endeavouring to modify his breathing. For example, TIRE (Test of Incremental Respiratory Endurance) is a package that determines maximum inspiratory pressure (MIP), which is related to inspiratory muscle strength; sustained maximum inspiratory pressure (SMIP) which reflects single breath work capacity, and Σ SMIP as a measure of inspiratory muscle endurance.
One application in which manipulation of breathing patterns by the application of controlled resistance to airflow could be potentially be enormously beneficial is in improving the delivery of pharmaceuticals from a nebuliser to a target area in the lungs. A major difficulty associated with inhalation drug delivery is in achieving specific and targeted deposition of the inhaled drug deep into the lung. In practice, many of the drug particles are deposited in the facemask of the nebuliser, in the mouth or in the upper airways, leading to high levels of drug wastage (often in the region of 60 to 80%) and the possibility of side effects. Improving the efficacy of delivery into the deep lung would allow the more economical and clinically effective use of a wide range of commonly used drugs such as antibiotics, anti-inflammatories and beta-agonists, as well as costly specialised drugs that require pulmonary delivery, such as interleukin 1 receptors, alpha antitrypsin, pulmozyme, gene therapeutics and interferons.
To date, most efforts have concentrated on particle size reduction to enhance deeper penetration into the lungs. However it is known that improved inhalation technique can also play a vital role in maximising effective deposition. For example, breath holding has some effect in allowing deposition deeper in the lung but there is a need for further development to exploit the potential of breathing control in this area.
Airway clearance is another therapeutic area where breathing technique is known to be of great importance. For example effective sputum clearance is vital in managing conditions such as cystic fibrosis. There is currently no general agreement as to which technique is most effective. A common theme of interventions such as the active cycle of breathing techniques, autogenic drainage and PEP therapy is the use of breathing from different lung volumes and augmenting shearing forces to facilitate movement of retained secretions from the lung periphery to central airways where they can be expectorated.
Devices which apply resistance to inspiration at the mouth, such as the RT2 device, have been found to be beneficial in increasing peripheral clearance by extending inspiratory time and prolonging intra-airway pressure status, so overcoming elastic recoil and delaying the onset of the equal pressure point.
Inspiratory muscle training is another potentially valuable therapeutic strategy, which has been applied successfully in several disease states and in training elite athletes. A strength/endurance response has been seen with reductions in blood lactate (an indicator of aerobic capacity). Again, however, the potential of the approach remains to be fully realised.
There therefore remains a continuing need for the development of improved devices for manipulating respiratory air flow, in particular for use in methods for providing targeted pulmonary drug deposition, airway clearance and respiratory muscle training.